JAK inhibitor baricitinib in moderate/severe COVID-19
9 December 2020. Related: COVID-19: investigational drugs, COVID-19.
Simon Collins, HIV i-Base
Several small studies have recently reported on using the anti-inflammatory drug baricitinib as a treatment for COVID-19 and larger studies are already underway.
The reports below are important for suggesting earlier evidence of potential benefit.
The largest of these included 113 patients at the Hospital of Prato in Italy and a control group of 78 matched for baseline characteristics including presenting symptoms and comorbidities.
Overall, baricitinib was associated with fewer deaths (0 vs 5) and fewer admissions to ICU (1 vs 14).
A small open-label VA study in Atlanta used single-dose baricitinib (2 to 4 mg) to treat 15 participants hospitalised with COVID-19 for its anti-inflammatory and potential off-target antiviral activity.
Participants needed to have pneumonia requiring oxygen support, moderate disease involving other organs or elevated/rising inflammatory markers.
Baseline inflammatory markers (including CRP, IL-6, and ESR) were elevated for all patients.
Baricitinib was associated with rapidly normalised temperature, reduced inflammation markers in 13/15 (86%) and clinical symptoms (need for supplementary oxygen) in 12/15 (80%) of participants. Three participants died.
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A 10-day course of remdesivir is expected to cost $2,340 in the US, while the cost of a baricitinib course is expected to be less than $500.
Although standard limitations include that this small cohort was not randomised and without a control arm cannot show a causal link, many larger studies are already ongoing.
These include at least a dozen smaller phase 2/3 studies and several larger phase 3/4 studies are already underway (n >1000 to 1500), including ACTT-2 and the UK TACTIC study. [3, 4, 5]
On 19 November 2020, the US FDA issued an emergency us authorisation for baricitinib in combination with remdesivir. [7]
This was based on baricitinib reducing recovery time compared to placebo, when used with remdesivir in the radndomised, double-blind, placebo controlled ACTT-2 study.
References
- Cantini et al. Retrospective, multicenter study on the impact of baricitinib in COVID-19 moderate pneumonia. Journal of Infection. (24 June 2020).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313480 - Titanji BK et al. Use of baricitinib in patients with moderate and severe COVID-19. Clinical Infectious Diseases, ciaa879, DOI: 10.1093/cid/ciaa879. (29 June 2020).
https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa879/5864596 - Stebbing J et al. Mechanism of baricitinib supports artificial intelligence‐predicted testing in COVID ‐19 patients. Embo Mol Med (2020), e12697. DOI: 10.15252/emmm.202012697. (24 June 2020).
https://www.embopress.org/doi/full/10.15252/emmm.202012697 - ClinicalTrials.gov. Adaptive COVID-19 Treatment Trial 2 (ACTT-2).
https://clinicaltrials.gov/ct2/show/NCT04401579 - ClinicalTrials.gov. Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia (CCAP).
https://clinicaltrials.gov/ct2/show/NCT04345289 - ClinicalTrials.gov. Multi-arm therapeutic study in pre-ICU patients admitted with COVID-19 – repurposed drugs (TACTIC-R) (TACTIC-R).
https://clinicaltrials.gov/ct2/show/NCT04390464 - US FDA. Coronavirus (COVID-19) Update: FDA authorizes drug combination for treatment of COVID-19. (19 November 2020).
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-combination-treatment-covid-19